K. Rózga-Wijas

Effect of surface modification of silica nanoparticles on toxicity and cellular uptake by human peripheral blood lymphocytes in vitro

Abstract Silica nanoparticles have an interesting potential in drug delivery, gene therapy and molecular imaging due to the possibility of tailoring their surface reactivity that can be obtained by surface modification. Despite these potential benefits, there is concern that exposure of humans to certain types of silica nanomaterials may lead to significant adverse health effects. The motivation of this study was to determine the kinetics of cellular binding/uptake of the vinyl- and the aminopropyl/vinyl-modified silica nanoparticles into peripheral blood lymphocytes in vitro, to explore their genotoxic and cytotoxic properties and to compare the biological properties of modified silica nanoparticles with those of the unmodified ones. Size of nanoparticles determined by SEM varied from 10 to 50 nm. The average hydrodynamic diameter and zeta potential also varied from 176.7 nm (+18.16 mV) [aminopropyl/vinyl-modified] and 235.4 nm (−9.49 mV) [vinyl-modified] to 266.3 (−13.32 mV) [unmodified]. Surface-modified silica particles were internalized by lymphocytes with varying efficiency and expressed no cytotoxic nor genotoxic effects, as determined by various methods (cell viability, apoptosis/necrosis, oxidative DNA damage, chromosome aberrations). However, they affected the proliferation of the lymphocytes as indicated by a decrease in mitotic index value and cell cycle progression. In contrast, unmodified silica nanoparticles exhibited cytotoxic and genotoxic properties at high doses as well as interfered with cell cycle.

Branched functionalised polysiloxane–silica hybrids for immobilisation of catalysts

Silica hybrids of functionalised polysiloxanes of well-defined structures, having various topologies (linear, comb-branched and dendritic-branched) and various densities of functional groups, were prepared. These hybrids were generated by the grafting of the polysiloxane to the prefunctionalised surface of porous silica particles. Polymers were obtained by living anionic ring opening polymerisation initiated by BuLi in THF of 2,4,6-trivinyl-2,4,6-trimethylcyclotrisiloxane, V3, 2-(diphenylphosphino)ethyl-2,4,4,6,6-pentamethylcyclotrisiloxane, PD2, and by copolymerisations of V3 with hexamethylcyclotrisiloxane, D3 and with 2-vinyl-2,4,4,6,6-pentamethylcyclotrisiloxane, VD2. Living polysiloxanes were terminated on the –CH2CH2SiMe2Cl groups present on the modified silica surface. Vinyl groups, besides being the destination for the immobilisation of the metalloorganic catalyst, were also the precursors for the generation of –CH2CH2SiMe2Cl groups used for the grafting of living polysiloxanes to build comb-branched and dendritic-branched polymers on the hybrid structures. Dendritic and comb polysiloxanes were also synthesised separately and were then attached to the silica particle surface functionalised with –CH2CH2SiMe2OSiMe2H groups. A Pt(II) complex was attached to the vinyl groups of the hybrids. A high catalytic activity of this complex was found in the test reaction of hydrosilylation of 1-hexene by PhMe2SiH.

Optically active dimethylsiloxane copolymers with nucleophilic chiral sulfur groups pendant to the polysiloxane chain

Polydimethylsiloxanes with part of the siloxane units bearing an optically active sulfoxide group were synthesized. These copolymers had chiral sulfur centres connected to the siloxane chain by a dimethylene bridge. They were obtained mostly by the kinetically controlled anionic ring-opening polymerization of 1-(2-organothioethyl)1,3,3,5,5-pentamethylcyclotrisiloxanes, followed by stereoselective oxidation of prochiral groups to yield partially enantiomeric sulfoxide groups. Sulfoxides bearing cyclic monomers were also used. Polymers were characterized by spectroscopy and polarimetry.

Polysiloxane–silica hybrids from novel precursors by the sol–gel process

1,1,1,7-Tetramethoxy-3,3,5,5,7,7-hexamethyl-1,3,5,7-tetrasiloxane {TMOS-D3} and 1,1,1,7-tetramethoxy-3,5,7-trimethyl-3,5,7-trivinyl-1,3,5,7-tetrasiloxane {TMOS-V3} were made, respectively, by cationic telomerisation of hexamethylcyclotrisiloxane (D3) or 2,4,6-trimethyl-2,4,6-trivinylcyclotrisiloxane (V3) with tetramethoxysilane (TMOS). These compounds were used as precursors of siloxane–silica materials. Their structure resulted in the generation of short trisiloxane segments which were well dispersed in the formed hybrid framework. These precursors or their mixtures with TMOS were subjected to sol–gel polycondensation in dispersions or in bulk catalysed by NaOH. Siloxane–silica hybrid materials were obtained either in the form of precipitated particles (1–80 µm) of various regular or irregular shapes or in the form of a monolithic material disintegrated on drying. In the sol–gel dispersion process, which was performed in the presence of a surfactant, cetyltrimethylammonium bromide, almost all methyl groups were converted to oxygen bridging two silicon atoms while in the bulk process a small fraction of unreacted alkoxyl and hydroxyl groups remained in the gel. Materials obtained from pure {TMOS-D3} and {TMOS-V3} showed a very low porosity and surface area. In contrast, particles having a high surface area can be obtained from mixtures of these new precursors and TMOS. Gels prepared from {TMOS-V3} and its mixture with TMOS were subjected to hydrosilylation with HMe2SiCl and the silylated particles were used for grafting of a living polysiloxane polymer.

Synthesis of the first POSS cage–anthracycline conjugates via amide bonds

Silsesquioxane derivatives widely used as polymer modifiers and catalytic supports have many interesting features making them potential nanocarriers in biomedicine. Two alternative synthetic routes were described, leading to the conjugates of functional POSS structures: octa(3-chloroammoniumpropyl)silsesquioxane and octa(carboxydecylthioethyl)silsesquioxane with anticancer drugs – anthracyclines.

Star-Shaped and Linear POSS-Polylactide Hybrid Copolymers

Novel octakis-2[(6-hydroxyhexyl)thio]ethyl-octasilsesquioxane (POSS-S-OH) as well as heptaisobutyl-2[(6-hydroxyhexyl)thio]ethyl-octasilsesquioxane (iBu-POSS-S-OH) were synthesized. POSS structures, bearing both types of groups i.e., 2[(6-hydroxyhexyl)thio]ethyl and the vinyl ones, pendant from the octahedral cage are also described. The synthetic pathway involved thiol-ene click reaction of 6-mercapto-1-hexanol (MCH) to octavinyloctasilsesquioxane (POSS-Vi), and heptaisobutylvinyloctasilsesquioxane (iBu-POSS-Vi), in the presence of 2,2′-azobisisobutyronitrile. The functionalized silsesquioxane cages of regular octahedral structure were used further as initiators for ring opening polymerization of l,l-dilactide, catalyzed by tin (II) 2-ethylhexanoate. The polymerization afforded biodegradable hybrid star shape and linear systems with an octasilsesquioxane cage as a core, bearing polylactide arm(s).

Condensation of α,ω-siloxane diols with aminoalkyl- (alkoxy)silanes

Kinetics of condensation of individual siloxane diols HO[(CH3)2SiO]xSi(CH3)2OH (x=3,5,6 and 9) with aminoalkyl-alkoxysilanes (RO)2SiR’(CH2)3NHR’’ (R = CH3, CH2CH3; R’ = CH3, OR; R’’ = H, (CH2)2NH2) is described. The second order rate constants point to the significant effect of the siloxane diols chain length on reactivity, which increases for higher homologues (almost an order) of magnitude on coming from x=3 to x=9. The role of substituents at silicon atom is discussed. Three novel functional siloxane oligomers (substrates) are described and characterized. Introduction Organopolysiloxanes bearing aminoalkyl substituents, often referred to as aminosiloxane oils, are a group of one of the most widely applied functionalized organopolysiloxanes [1,2,3]. Because of their unique properties, they have been used in both textile and hair care applications for decades [4-8]. These organoreactive silicones have gained also a large importance in certain other areas,such as treatment of metal [9] and mineral surfaces [10]. One of the simplest routes leading to synthesis of polyorganosiloxanes bearing aminoalkyl groups is condensation of aminoalkylmethoxymethylsilanes of a general formula RSiMex(OMe)3-x {R = [H2N(CH2)3] or [H2N(CH2)2NH(CH2)3; x = 0-1]} with mixtures of hydroxy-terminated siloxanes HOMe2SiO(Me2SiO)nSiMe2OH, n=1-15 [2]. Although condensation involving silanol groups has been extensively studied in the past [11,12], leading to understanding mechanistic pathways and structure reactivity relationship, the condensation of amino-functionalized alkoxysilanes with polysiloxanediols is described almost exclusively in patent literature. This literature concentrates on applied studies of the effect of structure of the final modified polysiloxane on such practical properties as wettability or softness of aminosiloxane oils treated materials [10,13]. In our early studies devoted to hydrophilic silicones [14] we have noted that the rate of condensation depends on the average molecular weight (chain length) of linear polysiloxane. Similar conclusion can be drawn from the work describing hydrogen bonding in poly(diorganosiloxane)-α,ω-diols [15] and patent data [2], judging, in the latter case, from reaction time and amine number of the relevant products.

Quaternary ammonium salt substituted polyhedral oligosilsesquioxanes (POSSes) as structure directing agents in the generation of porous silica materials

Abstract The sol-gel base catalysed hydrolytic polycondensations of tetramethoxysilane (TMOS) were studied in the presence of quaternary ammonium chloride substituted polyhedral oligosilsesquioxanes (POSSes): octa{3-[(2- hydroxyethyl)dimethylammonio]propyl chloride}octasilsesquioxane or octa[3-(noctyldimethylammonio) propyl chloride]octasilsesquioxane. Small amounts of these POSSes added to the sol-gel system markedly affected the morphology of the silica gel polycondensation products. The morphology was highly dependent on the POSS concentration. Amorphous mesoporous silica gels were obtained showing a high porosity and the surface area up to 615 m2g-1. Most of gels had a fairly large average pore diameters, 4-11 nm and pore volume 0.4-1.3 cm3g-1. TMOS having inserted hexamethyltrisiloxane chain, 1,1,1,7-tetramethoxyhexamethyltetra siloxane, (TMOSD3) in the mixture with TMOS was also used as the monomer in the sol-gel polycondensation; but obtained gels showed a low porosity.

Alkoxymethylcyclosiloxanes - new efficient precursors of crystalline (CH3SiO3/2)8 silsesquioxane and polymethyl silsesquioxanes

Abstract A new, highly efficient and very simple method for the synthesis of pure octahedral methylsilsesquioxanes (CH3SiO3/2)8, from cyclic 2,4,6,8-tetraalkoxy- 2,4,6,8-tetramethylsiloxane, was developed. We have found that T8Me can be synthesized from a mixture of alkoxymethylcyclosiloxane isomers in the hydrolytic condensation process, utilizing an ionic catalyst - tetrabutylammonium fluoride (TBAF). The reaction was carried out under very mild conditions, at room temperature, in a variety of solvents of different polarity. A substantial solvent effect was observed. THF helped in the formation of pure T8Me, whereas in other solvents mixtures of T8Me and poly(methylsilsesquioxanes) (PMQS) of substantial degree of regularity, were obtained.